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M. Perol
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MINI 16 - EGFR Mutant Lung Cancer 2 (ID 130)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:G.J. Riely, M.C. Garassino
- Coordinates: 9/08/2015, 16:45 - 18:15, Four Seasons Ballroom F3+F4
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MINI16.03 - Dose Optimization of Rociletinib for EGFR Mutated NSCLC (ID 967)
16:55 - 17:00 | Author(s): M. Perol
- Abstract
- Presentation
Background:
Rociletinib (CO-1686) is a novel, oral, irreversible mutant selective tyrosine kinase inhibitor for the treatment of patients with mutant epidermal growth factor receptor (EGFR) non-small cell lung cancer (NSCLC). Rociletinib has demonstrated efficacy against activating mutations (L858R and Del19) and the dominant acquired resistance mutation (T790M), while sparing wild-type EGFR. A maximum tolerated dose was not identified in Phase 1 with 1000 mg BID the highest dose studied. Here we assess the efficacy and safety of the three doses of rociletinib (500 mg BID, 625 mg BID and 750 mg BID) selected for Phase 2 study.
Methods:
TIGER-X (NCT01526928) is a Phase 1/2 open-label, safety, pharmacokinetics and preliminary efficacy study of rociletinib in patients with advanced EGFR mutant NSCLC progressing after ≥1 EGFR tyrosine kinase inhibitor (TKI). Efficacy is assessed using RECIST. Safety is evaluated using standard adverse event (AE) reporting.
Results:
As of April 2015, a total of 231 central T790M positive patients were evaluable for efficacy and 343 for safety (any T790M). All patients were enrolled in the USA (85%), Europe (9%) and Australia (6%). Baseline characteristics were similar in each dose group. The median number of prior therapies was 2. 85% had EGFR TKI as their most recent prior therapy and 10% had a history of diabetes/hyperglycemia. Immature ORRs are 53% (500 mg BID), 52% (625 mg BID) and 43% (750 mg BID), with disease control rates of 89% (500 mg BID), 87% (625 mg BID) and 82% (750 mg BID). The most common ≥grade 3 treatment-related AE was hyperglycemia [16% (500 mg BID), 25% (625 mg BID) and 35% (750 mg BID)] which was managed with oral hypoglycemic agents. Only one patient discontinued the study for hyperglycemia. Grade 3 QTc prolongation was uncommon, occurring in 2% (500 mg BID), 7% (625 mg BID) and 10% (750 mg BID) of patients, and demonstrated a relationship to dose. There were no clinically relevant cutaneous toxicities with 7 cases of grade 1 rash and 4 cases of grade 1 stomatitis (no dose relationship) and no paronychia.
Conclusion:
All 3 Phase 2 doses of rociletinib are active and well tolerated in a Western patient population with advanced NSCLC. The lack of cutaneous toxicities confirms the selectivity of rociletinib for mutant forms of EGFR and is an important contributor to QOL and maintaining dose intensity (Lacouture et al. 2011). Overall, the adverse event frequency appears to be related to dose, but antitumor activity does not, thus the risk/benefit profile may be optimal at the lowest dose studied.
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MINI 30 - New Kinase Targets (ID 157)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:K. Park, M. Villalona
- Coordinates: 9/09/2015, 18:30 - 20:00, Four Seasons Ballroom F3+F4
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MINI30.07 - Crizotinib in Patients with ROS1 NSCLC. Preliminary Results of the AcSé Trial (ID 2426)
19:05 - 19:10 | Author(s): M. Perol
- Abstract
- Presentation
Background:
To avoid uncontrolled off-label use and allow for a nationwide safe access to crizotinib (crz) for patients (pts) with an ALK, MET or ROS1 positive (+) tumor, the French National Cancer Institute (INCa) launched the AcSé program, funding both access to tumor molecular diagnosis and an exploratory multi-tumor 2-stage design phase II trial. We report the preliminary results of the ROS1+ NSCLC cohort.
Methods:
ROS1 status was assessed in 28 regional INCa molecular genetic centers by break-apart FISH assays in tumor samples showing an IHC score of ≥1+. Pts with ROS1 rearrangements, progressing after at least one standard treatment (including a platinum-based doublet, unless pts were considered as unfit for chemotherapy) were proposed to receive crz 250 mg BID. Responses were centrally assessed using RECIST v1.1. The objective response rate (ORR) and disease control rate (DCR) were assessed every 8 weeks.
Results:
From Aug. 5, 2013 to Mar. 1, 2015, 39 pts with ROS1+ NSCLC were enrolled. 37 pts had received crz, leading to 37 pts with clinical information. Median age: 62 years (range 33–81), 70% females, 95% non-squamous histology, and 94% metastatic disease at study entry. Median number of prior treatments: 2 (range 1 –7). Twenty four pts were still on treatment at the cut-off date, 13 have stopped crz (8 PD, 3 adverse events (AEs), 2 deaths). Among the 27 pts evaluable for response at 8 weeks, we observed 16 PR, 7 SD and 4 PD, leading to ORR=59% [95% CI:39-78], and DCR=85% [66-96]. DCR at 6 months was 57% (disease control was achieved in 12/21 evaluable pts). Crz was well tolerated with only 4 grade ≥3 (1 AE + 3 SAEs) and 9 grade 1-2 SAEs. Most common AEs, mainly grade 1, were visual disorders (54% of pts), peripheral edema (51%), diarrhea (48%), nausea (46%), and elevated transaminases (43%).
Conclusion:
Crz was well tolerated and achieved a robust treatment response rate in ROS1+ NSCLC. These results underline the interest of integrating ROS1 in biomarkers routine screening. Survival data and duration of response will be presented.
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ORAL 33 - ALK (ID 145)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:S. Gadgeel
- Coordinates: 9/09/2015, 16:45 - 18:15, Mile High Ballroom 1a-1f
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ORAL33.01 - Crizotinib Outcome and Post-Progression Management in ALK+ NSCLC: IFCT-1302 CLINALK (ID 1355)
16:45 - 16:56 | Author(s): M. Perol
- Abstract
- Presentation
Background:
Phase III trials have demonstrated the superiority of the ALK tyrosine kinase inhibitor (ALK-TKI) crizotinib compared to standard chemotherapy in advanced ALK positive non-small cell lung cancers (ALK+ NSCLC) in first line and second line setting. Objective response rate (ORR) with crizotinib ranged from 65 to 75% and median progression free survival (PFS) from 7.7 to 10.9 months. However a resistance to crizotinib always occurs. The French Cooperative Thoracic Intergroup (IFCT)-1302 CLINALK study aimed to describe clinical outcome and post-progression management in a large cohort of French patients with ALK+ NSCLC treated with crizotinib.
Methods:
IFCT-1302 CLINALK is a multicentric observational retrospective study. Patients with ALK+ NSCLC from centers of the IFCT network were included according to the main following criteria: advanced stage III or stage IV NSCLC, ALK immunochemistry (IHC) and/or ALK FISH positivity, crizotinib treatment in the setting of the French expanded access cohort program or as approved drug. Epidemiological and clinical data, crizotinib efficacy (objective response based on RECIST, PFS, overall survival (OS)), duration of treatment with crizotinib after disease progression and post progression outcome were collected on a case report form. The study inclusion period was from November 18 2011 to December 31 2013. The data cut-off was December 31 2014.
Results:
318 patients were included (median age 58.3, female 49.4%, caucasian 98.6%, non-smoker 55.1%, performance status 0/1 78.7%, adenocarcinoma 91.7%, stage III 14.5%, stage IV 85.5%, brain metastasis 35.9%). IHC was positive in 151/173 patients and FISH in 279/283 patients. Before crizotinib treatment, patients received platinum-based chemotherapy in 89% of cases and pemetrexed-based chemotherapy in 76.1%. Crizotinib was prescribed as first-line treatment in 17 patients (5.3%), second-line in 168 patients (52.8%), third-line in 58 patients (18.2%) and more than third-line in 75 patients (23.7%). Objective response was complete response in 1 patient (0.3%), partial response in 126 patients (40.0%), stable disease in 62 patients (19.7%) and progression in 58 patients (18.4%). ORR was 40.3 % (95%CI, 34.9-45.7). 262/318 patients presented progressive disease (82.4%) at time of analysis. Median PFS was 6.9 months (95%CI, 5.7-8.6). Median OS with crizotinib was 18.7 months (95%CI, 15.2-22.5). Median duration of treatment with crizotinib after disease progression was 56 days (29-203). Among 143 patients with subsequent treatments, crizotinib was rechallenged in 32 patients (22.4%). 58/143 patients (40.6%) were treated after crizotinib failure with another ALK-TKI, either alectinib (19/58, 32.8%) or ceritinib (40/58, 69.0%). The ALK-TKI sequence was crizotinib-alectinib in 18 patients, crizotinib-ceritinib in 39 patients and crizotinib-alectinib-ceritinib in 1 patient.
Conclusion:
This retrospective study of 318 patients with ALK+ NSCLC showed a remarkable efficacy of crizotinib, with a 18.7 months median OS, a 40.3% ORR and a 6.9 months median PFS. However, ORR and mPFS were lower than those reported in phase III trials, which may be due to less stringent selection criteria. Analysis of predictive factors of response and survival including post-progression strategies will be presented.
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P1.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 206)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.01-086 - TIGER-3: A Phase 3 Open-Label, Randomized Study of Rociletinib vs Chemotherapy in NSCLC (ID 949)
09:30 - 09:30 | Author(s): M. Perol
- Abstract
Background:
Rociletinib (CO-1686) is a novel, oral, irreversible tyrosine kinase inhibitor for the treatment of patients with mutant epidermal growth factor receptor (EGFR) non-small cell lung cancer (NSCLC) that has demonstrated efficacy against the activating mutations (L858R and Del19) and the dominant acquired resistance mutation (T790M), while sparing wild-type EGFR. TIGER-X, a Phase I/II dose-ranging trial, has provided evidence that rociletinib is associated with durable response and is well tolerated in patients with NSCLC and positive T790M status following progression on a TKI.[1 ]Efficacy has also been noted for patients with T790M negative status in TIGER-X.[2] TIGER-3 is designed to investigate single agent rociletinib vs chemotherapy in patients who have failed EGFR therapy and platinum-based doublet chemotherapy, which is a setting of acquired resistance and high unmet need for targeted therapeutic options. TIGER-3 will evaluate patients with T790M positive and negative status based on tumor biopsies and plasma, and biomarkers of response and/or resistance.
Methods:
Patients with histologically or cytologically confirmed metastatic or unresectable locally advanced NSCLC, with radiological progression on the most recent therapy will be enrolled in this phase 3, randomized, open-label study (NCT02322281). Patients must have documented evidence of a tumor with ≥1 EGFR activating mutations excluding exon 20 insertion, and prior treatment with an EGFR TKI and platinum-containing doublet chemotherapy. Patients will be randomized 1:1 to receive rociletinib twice daily (500 mg) or single agent cytotoxic chemotherapy (investigator choice specified before randomization) until disease progression according to RECIST 1.1. Patients will be stratified by presence or absence of brain metastases, ECOG performance status (0 vs 1), and race (Asian vs non-Asian). The primary endpoint is progression-free survival (PFS). Secondary endpoints include safety, objective response rates, duration of response, disease control rate, and overall survival. Kaplan-Meier methodology will assess time to event variables. The stratified log-rank and the hazard ratio will be used for comparing PFS distributions. Serial assessment of safety will be carried out based on standard adverse event reporting. Planned enrolment is 600 patients; enrolment has been open since March 2015. Sequist LV J Clin Oncol. 2014 Soria J-C EORTC-NCI-AACR 2014
Results:
Not applicable
Conclusion:
Not applicable
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P3.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 208)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.01-043 - Assessing Treatment Strategies for Lung Cancer in Octogenarians: Insights From a Cohort of 337 Patients (ID 1216)
09:30 - 09:30 | Author(s): M. Perol
- Abstract
Background:
Aging increases the incidence of lung cancer in octogenarians. In this population, only limited data about treatment strategies and results are available, as those patients are usually not eligible for clinical trials; meanwhile, previously reported cohorts mostly focused on early-stage tumors. Our objective was then to provide a global picture of the treatment strategies for lung cancer in octogenerians, and to parallel those with available standards.
Methods:
Retrospective observational study of all consecutive patients aged 80 or more, with pathologically-confirmed lung cancer, and diagnosed at the Hospices Civils de Lyon between January 2005 and April 2014.
Results:
337 patients were included, 298 (88%) with non-small cell lung cancer (NSCLC), and 39 (12%) with small-cell lung cancer. For NSCLC, tumor was stage I, II, III, and IV in 10%, 9%, 25% et 57% of cases, respectively. Overall survival was 8.4 months. Geriatric assessment had been done only for 11% of patients. Overall, a standard treatment strategy - i.e. based on available recommendations and guidelines - was conducted for 42% of patients, while 24% received non-standard treatment, and 34% best supportive care only. At multivariate analysis, favorable prognostic factors on overall survival were performance status 0-1 (p<0.001), stage I/II (p<0.001), adenocarcinoma histology (p=0.026), and a standard treatment strategy (p<0.001). In the setting of metastatic NSCLC, 35% of patients received chemotherapy, the most frequent regimen being carboplatine and paclitaxel.
Conclusion:
Octogenarians with lung cancer are eligible for antitumor treatment in nearly 70% of cases, consisting of standard, recommended therapy in about half of the cases. Our data provide a unique overview of the management of octogenarians with lung cancer, to foster future prospective studies dedicated to this subset of patients.
